The present invention relates to a method for preventing senescence, particularly bone senescence, which method comprises administering 24,25-dihydroxy cholecalciferol in a pharmaceutically effective amount.
The present invention relates further to a method for increasing bone mass, namely a method for increasing bone volume and increasing bone strength, which method comprises administering 24,25-dihydroxy cholecalciferol in a pharmaceutically effective amount.
In Japan, population of the aged 65 years or over old is steadily increasing at a rate far greater than that in any other foreign country. It has been demonstrated that the bone volume in the aged tends physiologically to decrease as they grow old. It is generally held that the bone volume of a person begins to decrease about when the person becomes forty. Thus, the decrease of bone volume serves as an index of senescence. The bones have a biological significance that they not only play a part of a mechanical support for the whole body but also serve as an important storehouse of calcium ions indispensable to homeostasis of the body. The decrease of bone volume due to senescence, therefore, constitutes itself a serious problem. No medicine safe and capable of preventing sencescence has been available to date.
Owing to the arrival of the so-called senile society in recent years, even when normal persons who do not specifically suffer from disorders in bone metabolism are aged, the aged tend to suffer from the aforementioned decrease of bone volume coupled with the physiological decrease of bone strength and, consequently, tend to suffer a fracture more readily under a feeble external force than in their younger days. In the aged, immobilized osteopenia advances quickly once they suffer a fracture. The increment of bone strength in the aged, therefore, is a very important task. In such circumstances, the development of a medicine safe and capable of increasing bone strength has been urgently expected.
The present inventors have continued a study as to a physiological activity of a substance inherently occurring in the body of a healthy person and exhibiting proven safety and as a result, found that 24,25-dihydroxy cholecalciferol (hereinafter referred to as "the present substance" or as "24,25-(OH).sub.2 -D.sub.3 ") possesses numerous physiologically activity. As concerns the bones, they have found that the present substance has an activity of preventing osteoporosis, i.e. one of the disorders in bone metabolism. As the result of their latest experiment on lifelong administration of the present substance to rats, they have found that the present substance has an activity of increasing bone volume (decrease of which is an index of senescence), without affecting the bone quality and thereby preventing senescence. One aspect of the present invention has been perfected based on the above findings. In an extension of the experiment, they have further found that a normal mammal to which the present substance is administered exhibits bone strength clearly surpassing the average bone strength of non-administered normal mammals, and as a result, another aspect of the present invention has been perfected. These findings are literally epochal in the light of the fact that the conventional pharmaceutical compositions for adjusting bone metabolism is found to be only capable of restoring bones having abnormality due to morbidity near to normality. Further, the method for increasing bone volume and the method for increasing bone strength according to the present invention can be effectively applied not only to aged mammals but also to adult mammals and infantile mammals.
When the present invention is applied to adult mammals and aged mammals, not only the bone mass thereof is increased but also the systemic senescence relative to the increment of bone mass is clearly prevented.
From the viewpoint of anti-senescence activity thereof, therefore, the findings which have culminated in the present invention are epochal in the true sense of the word.
The first object of the present invention is to provide a method for preventing senescence, comprising administering 24,25-dihydroxy cholecalciferol in a pharmaceutically effective amount.
The second object of the present invention is to provide a method for increasing bone volume, comprising administering 24,25-dihydroxy cholecalciferol in a pharmaceutically effective amount.
The third object of the present invention is to provide a method for increasing bone strength of a normal mammal, comprising administering 24,25-dihydroxy cholecalciferol in a pharmaceutically effective amount.
The fourth object of the present invention is to provide use of 24,25-dihydroxy cholecalciferol for preparing anti-senescent compositions.
The fifth object of the present invention is to provide use of 24,25-dihydroxy cholecalciferol for preparing compositions for increasing bone volume.
The sixth object of the present invention is to provide use of 24,25-dihydroxy cholecalciferol for preparing compositions for increasing bone strength of a normal mammal.